Clinical Evaluation of Pipecuronium Bromide and Its Comparison With

<ul style="display: flex;"><li style="flex:1">Scholars Journal of Applied Medical Sciences (SJAMS) </li><li style="flex:1">ISSN 2320-6691 (Online) </li></ul>ISSN 2347-954X (Print) Sch. J. App. Med. Sci., 2013; 1(6):943-950 ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) <a href="/goto?url=http://www.saspublisher.com/" target="_blank">www.saspublisher.com </a>Research Article Clinical Evaluation of Pipecuronium Bromide and its Comparison with Pancuronium Bromide Kaushal RP Associate Professor, Department of cardiac anesthesia, Gandhi Medical College, Bhopal, India. *Corresponding author Kaushal RP Email: Abstract: The study was carried out to compare the intubating conditions, cardiovascular responses, neuro-muscular blocking properties and reversal characteristics of pipecuronium bromide and pancuronium bromide. This is a prospective hospital based study. 100 patients belonging to ASA grade I or II physical status aged 18 to 70 years were divided into two groups of 50 patients each. Group 1 received pipecuronium bromide in the dose of .08 mg / kg and group 2 patients received pancuronium bromide in dose of 0.1 mg/kg. Each patient was pre medicated uniformly. Time for onset of apnoea for pipecuronium and pancuronium were 91.64+ 3.59 sec. and 118.84 + 12.53 sec. respectively. The mean time for intubation was 126.60 +12.55 sec. and 144.60 + 22.87 sec. with pipecuronium and pancuronium respectively. Mean duration of block for pipecuronium was 78.64 + 8.97 min. the block for pancuronium lasted from +36-40 min with a mean duration of block 41.60+ 5.57 min. The mean duration of maintenance dose in pipecuronium cases was 45.08 + 7.19 min., while it was 27.06 + 5.01 min in pancuronium cases. Pipecuronium patients did not show significant hemodynamic changes while hemodynamic changes were seen with pancuronium patients due to mild atropine like and sympathomimetic action of pancuronium. There was no spontaneous recovery in both groups of patients. All patients required titrated dosage of atropine / neostigmine. In pipecuronium patients, after reversal, 90% of patients had adequate recovery and scored a high score between 11-15. In pancuronium patients, after reversal, 88% had adequate recovery and scored a high score between11-15. It is evident that pipecuronium bromide provided excellent intubating conditions, negligible cardiovascular disturbances, longer duration of action, lack of cumulative action, easy reversibility of neuromuscular block with high postoperative recovery score. Thus it proves to be the ideal muscle relaxant of choice in the long surgical procedure. Keywords: pipecuronium, pancuronium, neuromuscular block As Curare became popular in anesthetic practice, search for other non depolarizing muscle relaxants without side effects of curare started. This lead to the development of series of non-depolarizing muscle relaxants. King synthesized metocurine in 1935 [2]. Alcuronium, pancuronium, Vecuronium, pipecuronium , Atracurium, Mivacurium and Rocuronium etc. were introduced later on in clinical anaesthesia [3]. INTRODUCTION The introduction of curare into clinical practice did not achieve immediate success. In USA and U.K., it was looked suspiciously in early fifties, use of neuromuscular blocking drug was associated with high mortality and its use in general was avoided. Initially, the high mortality was attributed to “high toxicity” or impurities of the drug but it was soon realized to be the improper use of curare. e.g. with ether and spontaneous ventilation without adequate control of breathing- could and did result in disaster. Later, when importance of controlled breathing and carbon dioxide elimination was established, the use of this drug became safe and the concept of triad of anesthesia or balanced anesthesia emerged. Subsequently purified curare like, tube curare, pipe curare, and intercostin etc were used. Aims and Objects •To compare and evaluate intubating conditions and responses to endotracheal pipecuronium intubation bromide with and pancuronium bromide. •To assess and compare the neuromuscular blocking characters of pipecuronium bromide and pancuronium bromide by employing – Evoked potential i.e. T.D.F. by peripheral nerve stimultior. An Ideal Muscle Relaxant should have the following requirements: Non-depolarising mechanism of action, Rapid onset of action, Intermediate duration of action, Rapid recovery, Non – Cumulative, Highly selective at the neuromuscular junction, No histamine release, High potency, Easily Reversible and Pharmacologically inactive metabolites [1]. •To compare cardiovascular effects of pipecuronium bromide and pancuronium bromide. 943 Kaushal RP, Sch. J. App. Med. Sci., 2013; 1(6):943 -950 carried for another 30 seconds and then upon availability of favorable conditions, intubation was performed. MATERIALS AND METHODS Present study entitled “Clinical evaluation of pipecuronium bromide and its comparison with Pancuronium bromide was carried in the "Department of Anaesthesiology MGM Medical College” Indore with an object to find out the neuromuscular blocking properties of pipercuronium bromoide recently introduced and to compare it with Pancuronium bromide. Ventilation of patient was continued with Oxygen and Nitrous oxide on circle absorber/Bain’s circuit. Every 10 min. the ulnar nerve was stimulated by TDF method and responses were noted. A degree of neuromuscular blockade upto extent of 90% resulted in disappearance of 4th response of TDF. Appearance of 4th response suggested waning of block to 50% which indicated the administration of supplementary dose to suppress 4 responses i.e. to achieve 90% blockade suitable for surgery. Thus, duration of action of supplementary dose was calculated as the time required for appearance of 4th response. Present study included 100 patients from wide range of age group (18 Yrs to 70 Yrs) were divided in two groups of 50 patients each. Group 1 patients received pipecuronium bromide in dose of .08 mg/kg and group 2 patients received pancuronium bromide in dose of 0.1 mg/kg. All the patients included in the study were subjected to thorough preoperative clinical examination and investigations to rule out systemic disease thus, the patients included in the study belonged to ASA grade I or II Physical status. Hemodynamic measurements (Pulse, B.P.) were taken just before administration of relaxant and just after muscle relaxant, after intubation, and then 10 mts. and 30 mts. Later. At the conclusion of surgery patient was reversed as usual with atropine and neostigmine. The later drug was given by titrating dose against TDF response till height of all the four contractions were same and patient clinically met criteria’s of reversal. Each patient was was premedicated uniformly as under : Inj. Artopine 0.01 mg/kg maximum of 0.6 mg/1/m. Inj. Pentazocine .5 mg/kg maxiumum of 30 mg/1/m. These drugs were administered intramuscularly about 45 minutes before induction of anesthesia. After arrival of patient in OT, besides intravenous lines, and other monitoring devices, peripheral nerve stimulators were placed in position to stimulate the ulnar nerve. Post operative recovery scoring was done periodically. Five parameters were taken into account and a score of 0, 1, 2, 3, was given for each parameter and points were graded as 7,8,9. High score (11-15) was safe for discharge but medium Score (6-10) needs further observation. Low Score ( 1-5) required intensive care and observation. The height of twitch response before relaxant was noted and all the four contractions were of almost same height. Patients were preoxygenated with 100% 02 for 3 min and induced with Pentothal sodium in appropriate dose intravenously. Prior intravenous injection of predetermined dose of muscle relaxant was given. The period of hypoventilation/ apnoea was covered with assisted ventilation. The time for appearance of apnoea was noted and recorded the twitch height. After 60 to 90 sec. of inj. of relaxant drug, assessment of conditions for laryngoscopy and Endotracheal intubation was made. In case of favorable conditions, endotracheal intubation was performed and in otherwise situations, further assisted ventilation was RESULTS All patients included in the study belonged to ASA grade 1 or 2 as per American society of anaesthetists classification. The patients were divided in two groups of 50 each. Groups 1 were given pancuronium bromide and group -2 were given pipecuronium bromide as muscle relaxants in narcotic analgesic sequence. The clinical observations made on these 100 patients have been tabulated from 1 to 16 Table 1: Age distribution among the patients (male/female) <ul style="display: flex;"><li style="flex:1">Age </li><li style="flex:1">Number of patient </li><li style="flex:1">Total </li></ul><ul style="display: flex;"><li style="flex:1">Male </li><li style="flex:1">Female </li></ul>< 20 21-30 31-40 41-50 51-60 61-70 15 11 12 06 03 00 47 <ul style="display: flex;"><li style="flex:1">4</li><li style="flex:1">19 </li></ul>25 25 19 09 14 13 13 06 03 53 03 <ul style="display: flex;"><li style="flex:1">100 </li><li style="flex:1">Total </li></ul>Majority of patients are between 21 to 30 years. Mean age observed was 35.53 Years. 944 Kaushal RP, Sch. J. App. Med. Sci., 2013; 1(6):943 -950 Table 2: Types of Surgical Procedure <ul style="display: flex;"><li style="flex:1">Types of PS operation </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Pipecuronium </li><li style="flex:1">Pancuronium </li></ul>General Surgery Neurosurgery Obst Surgery Gynaecology Orthopaedics Total 24 17 00 03 06 50 16 03 03 07 21 50 Table 3: Shows time for onset of apnoea <ul style="display: flex;"><li style="flex:1">Time for Onset of Apnoea </li><li style="flex:1">Pipecuronium </li><li style="flex:1">Panucuronium </li></ul><ul style="display: flex;"><li style="flex:1">< 60 sec </li><li style="flex:1">00 </li></ul>38 (76%) 12 (24%) 00 00 00 33(66%) 17(34%) 00 61 and 90 sec 91 and 120 121 and 150 <ul style="display: flex;"><li style="flex:1">151 and 180 </li><li style="flex:1">00 </li></ul>Mean Apnoes time onset ±S.D. 91.64 ±3.59 sec 118.84 ±12.53 sec Pipecuronium was administered in group -I. In 76% In Group II, in 66% patient’s apnoea occurred in 90- 120 sec. and in 34% occurred in 120-150 sec. The mean time for onset of apnoea was 118-84 ±12.53 sec. patient’s apnoea occurred in 60-90 sec and in 24% occurred in 90-120 sec. The mean time for onset of apnoea was 91.64 ±3.59 Sec. Table 4: Intubating Time <ul style="display: flex;"><li style="flex:1">Number of Cases </li><li style="flex:1">Time ( Sec.) </li></ul><ul style="display: flex;"><li style="flex:1">Pipecuronium </li><li style="flex:1">Pancuronium </li></ul><ul style="display: flex;"><li style="flex:1">0</li><li style="flex:1">60 – 90 </li></ul>91 – 120 121 – 150 151 – 180 0 39 (70%) 11 (22%) 00 15 (30%) 29 (58%) 06 (12%) Mean apnoea time Onset + S.D. 126.60+12.55sec. 144.60 +22.87 sec. <ul style="display: flex;"><li style="flex:1">78% patients of group 1 easily intubated within </li><li style="flex:1">126.60 + 12.55 second. 30% patients of group-ll </li></ul>intubated after 15-180 sec. of pancuronium administration. The mean time for favorable intubation in Group II was e 144.60 + 22.87 second. 120 sec. after injection of pipecuronium. Rest 22% required slightly longer to facilitate easy intubation. The mean time for favorable intubation in Group 1 was Table 5: Incidence of Intubating Difficulty Grade Excellent Satisfactory Fair <ul style="display: flex;"><li style="flex:1">Score </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Pipecuronium </li><li style="flex:1">Pancuronium </li></ul>42 (84%) 08 (16%) 00 03 02 01 00 49 (98%) 01 (2%) 00 <ul style="display: flex;"><li style="flex:1">Impossible </li><li style="flex:1">00 </li><li style="flex:1">00 </li></ul>Table No. 5 shows incidence of intubation difficulty. The grading system followed in the present study was as suggested by Lund and Stovner (1962). Pipecuronium provided excellent intubating conditions in 98% patients and in 2% patients, satisfactory conditions. Pancuronium provided excellent intubating conditions in 84% and in 16% satisfactory conditions. In none of the case from either group we failed to intubate the patient. Table 6: Mean Pulse Rate Mean Pulse Rate Pre Operative Just after muscle Relaxant After Intubation 10 Mts. After <ul style="display: flex;"><li style="flex:1">Pipecuronium </li><li style="flex:1">Pancuronium </li></ul>91.92 (+6.75) 101.36 (+8.88) 105.16 (+7.35) 101.64 (+7.39) 98.96 (+7.40) 97.00 (+6.27) 94.56 (+ 13.87) 94.80 (+11.27) 97.94 (+12.33) 94.88 (+11.27) 94.92 (+11.48) 94.88 (+11.27) 20 Mts. After 30 Mts. After 945 Kaushal RP, Sch. J. App. Med. Sci., 2013; 1(6):943 -950 Table 7: Blood Pressure Mean Systolic in Blood Pressure in mm-Hg Pipecuronium 119.20 (+ 13.42) Just after muscle Relaxant 119.60 (+13.22) Pancuronium 113.40 (+12.17) 126.10 (+13.08) 132.90 (+12.10) 125.92 (+11.11) 124.98 (+10.28) 121.20 (+10.92) Pre Operative After Intubation 10 Mts. After 20 Mts. After 30 Mts. After 121.60 (+12.99) 119.20 (+12.06) 121.40 (+12.23) 119.60 (+12.01) Table No. 6 and 7 shows the study of cardiovascular parameters made preoperatively, just after injection of muscle relaxant, after intubation and at every 10 Mins. till the end of surgery. Table 8(a): Duration of Initial Dose of Pipecuronium Duration in mts. Upto 60 Mts. Number of Patients Pipecuronium 02 <ul style="display: flex;"><li style="flex:1">61 – 70 mts. </li><li style="flex:1">12 </li></ul>71 – 80 mts. 81 – 90 mts. 14 20 <ul style="display: flex;"><li style="flex:1">91- 100 mts. </li><li style="flex:1">02 </li></ul><ul style="display: flex;"><li style="flex:1">Mean apnoea time Blocks + S.D. </li><li style="flex:1">78.64+8.97 </li></ul>Table 8(b): Duration of Action Initial Dose <ul style="display: flex;"><li style="flex:1">Duration in Mts. </li><li style="flex:1">Number of Patients Pancuronium </li></ul><ul style="display: flex;"><li style="flex:1">Less than 20 </li><li style="flex:1">0</li></ul><ul style="display: flex;"><li style="flex:1">20 – 25 </li><li style="flex:1">01 </li></ul><ul style="display: flex;"><li style="flex:1">26 – 30 </li><li style="flex:1">01 </li></ul><ul style="display: flex;"><li style="flex:1">31 – 35 </li><li style="flex:1">08 </li></ul>36 – 40 41 – 45 46 – 50 19 13 08 <ul style="display: flex;"><li style="flex:1">Mean apnoea time Initial + S.D. </li><li style="flex:1">41.60+5.57 sec. </li></ul>Table No. 8 (a & b) shows the duration of action of the initial dose of pipecuronium and Pancuronium. Table 9: Duration of Maintenance Dose Pipecuronium <ul style="display: flex;"><li style="flex:1">Duration in Mts. </li><li style="flex:1">Pipecuronium </li></ul>Upto 30 Mts. 31 – 40 mts. 41 – 50 mts. 51 – 60 mts. 61- 70 mts. 00 16 23 11 00 Total number of patients Mean apnoea time + S.D. 50 45.08+7.19 Table 10: Duration of Maintenance Dose Pancuronium Duration In Mts. Upto 15 Mts. 16 – 20 mts. 21 – 25 mts. 26 - 30 mts. Pancuronium 00 09 20 12 <ul style="display: flex;"><li style="flex:1">09 </li><li style="flex:1">31- 35 mts. </li></ul>Total number of patients Mean apnoea time + S.D. 50 27.06+5.01 946 Kaushal RP, Sch. J. App. Med. Sci., 2013; 1(6):943 -950 Table 11: Reversal Character <ul style="display: flex;"><li style="flex:1">Dose of Neostigmine Required </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Pipecuronium </li><li style="flex:1">Pancuronium </li></ul>Spont Recovery <ul style="display: flex;"><li style="flex:1">05 mg </li><li style="flex:1">0</li></ul>0 0<ul style="display: flex;"><li style="flex:1">0</li><li style="flex:1">1 mg </li></ul><ul style="display: flex;"><li style="flex:1">1.5 mg </li><li style="flex:1">0</li><li style="flex:1">0</li></ul><ul style="display: flex;"><li style="flex:1">2 mg </li><li style="flex:1">0</li><li style="flex:1">0</li></ul><ul style="display: flex;"><li style="flex:1">2.5 mg </li><li style="flex:1">50 </li><li style="flex:1">50 </li></ul>Table 12: Recovery Score of Group I Patients in whom Reversal was done in O.T. <ul style="display: flex;"><li style="flex:1">Recovery Score </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Just After Reversal </li><li style="flex:1">10 Mts. Later </li></ul>Spont Recovery 11- 15 06 – 10 01 – 05 Total 44 06 00 50 50 00 00 50 Table 13: Recovery Score in Recovery Room (Group 1 Patient) Recovery Score Number of Patients <ul style="display: flex;"><li style="flex:1">Arrival in R.R. </li><li style="flex:1">30 mts. Later </li></ul>Spont Recovery <ul style="display: flex;"><li style="flex:1">11- 15 </li><li style="flex:1">50 (100%) </li><li style="flex:1">50 (100%) </li></ul>06 – 10 01 – 05 Total 00 00 50 00 00 50 Table 14: Recovery Score in O.T. in whom Reversal was done (Group II Patients) <ul style="display: flex;"><li style="flex:1">Recovery Score </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Arrival In R.R. </li><li style="flex:1">30 mts. Later </li></ul>Spont Recovery <ul style="display: flex;"><li style="flex:1">11- 15 </li><li style="flex:1">45 (100%) </li><li style="flex:1">50 (100%) </li></ul>06 – 10 01 – 05 Total 00 00 50 00 00 50 Table 15: Recovery Score in Recovery Room (Group II Patients) <ul style="display: flex;"><li style="flex:1">Recovery Score </li><li style="flex:1">Number of Patients </li></ul><ul style="display: flex;"><li style="flex:1">Arrival in R.R. </li><li style="flex:1">30 mts. Later </li></ul>Spont Recovery <ul style="display: flex;"><li style="flex:1">11- 15 </li><li style="flex:1">50(100%) </li><li style="flex:1">50 (100%) </li></ul>06 – 10 01 – 05 Total 00 00 50 00 00 50 were included in this study. All patients belonged to ASA grade I and II. DISCUSSION The present study was undertaken with an object to evaluate efficacy of Pipecuronium bromide and to compare it with pancuronium bromide. Intubating Conditions In 76% patients, who received pipecuronium, the time for onset of apnoea was between 61 to 90 seconds and in 24% cases, it was between 91 to 120 seconds. The mean apnoea time was 91.64 seconds 13.59 sec. In 78% patients, the intubating time was between 91 to 120 seconds and in 22% cases, it was 121 to 150 seconds. The mean intubating time was 126.60 seconds +12.55 seconds. In our study, we have compared the intubating conditions, hemodynamic changes and reversal conditions of pipecuronium bromide and Pancuronium bromide. Total hundred patients of various age groups and both sexes, scheduled for various surgical interventions 947 Kaushal RP, Sch. J. App. Med. Sci., 2013; 1(6):943 -950 The finding of our study is supported by those of Kelman and Kennedy [7], who studied the cardiovascular effects of pancuronium in men. They demonstrated that pancuronium does cause a marked rise in the heart rate accompanied by a lesser increase in cardiac output and mean arterial pressure. The intubating conditions were excellent in 98% cases and satisfactory in 2% cases. Our findings corelate with these of the following workers. Lirijani et al. used this drug in a dose of 70 to 85 micro gram/ kg. Body weight and found complete block <ul style="display: flex;"><li style="flex:1">in 2 to 2.5 mts. [4]. </li><li style="flex:1">Brankay et al. [8] reported that a potency of </li></ul>pipecuronium is similar to pancuronium bromide with <ul style="display: flex;"><li style="flex:1">minimal cardiovascular effects. </li><li style="flex:1">Tassonyi E et al., found that the intubation can be </li></ul>carried out within 23 minutes, where 70 to 80 micro <ul style="display: flex;"><li style="flex:1">gram/kg. body weight is given [13]. </li><li style="flex:1">Bunjatjian A.A et al., [9] concluded that unlike </li></ul>pancuronium however pipecuronium had no unwanted circulatory side effects. Boros M et al. [10] made similar observation. Azad SS et al. concluded that pipecuronium has relatively rapid onset and trachea could be intubated successfully in 1.5 minutes with a dose of either 0.07 <ul style="display: flex;"><li style="flex:1">mg/kg body with or 0.10 mg/kg body wt. [6]. </li><li style="flex:1">Tassonyi E et al. [13] reported that the main </li></ul><ul style="display: flex;"><li style="flex:1">advantage of pipecuronium is that, </li><li style="flex:1">It has no </li></ul>When pipecuronium was used, the mean time for onset of apnoea was 118.84 +12.53 seconds. Intubation was not possible before 90 seconds in any of the patients. 30% patients could be intubated between 91 to 120 seconds, 58% between 121 to 150 seconds and 12% between 151 to 180 seconds. The mean intubation time was 144.60 +22.8 seconds. cardiovascular side effects as has also been proven with invasive methods.

Clinical Evaluation of Pipecuronium Bromide and Its Comparison With

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